We are studying the molecular mechanisms involved in age-dependent thymic involution and T-cell aging. We have demonstrated that expression of beta-catenin in thymocytes in CAT-Tg mice results in accelerated age-dependent thymic involution and aging. ? ? Recent analysis showed that expression of beta-catenin inhibits proliferation of developing thymocytes and causes DNA damage. Developing thymocytes also have oncogene-induced-senescence (OIS) and undergo p53-dependent apoptosis. This is the reason expression of the powerful oncogene, beta-catenin does not result in thymic tumors. With regards to the observation that expression of beta catenin accelerated thymic involution, in the coming year we plan to establish if DNA damage, OIS and p53-dependent apoptosis are features of normal aging in wild type mice.
